Xiaobo Mao is exploring the role of prion-like proteins in the pathogenesis of neurodegeneration, including protein misfolding strains and structures, pathology spread, neurotoxicity, and neuroinflammation. Emerging evidence has shown that prion-like protein spreading is the driver to pathogenesis. Mao has pioneered new understandings of pathogenic α-syn cell-to-cell transmission. He has identified that lymphocyte-activation gene 3 (LAG3) is an essential receptor that mediates the internalization of α-syn preformed fibrils (PFF) (Science 2016, PNAS 2021), and deletion and inhibition of LAG3 significantly impede α-syn pathology spread. His team is selected as one of the 40 key discoveries in 200-years Parkinson’s disease basic research. His team found that amyloid-β precursor-like protein 1 (APLP1) as a LAG3 co-receptor facilitates the neuronal uptake of α-syn PFF. Internalized PFF further induces the activation of poly(ADP-ribose) polymerase 1 (PARP1) and PAR accumulation, converting α-syn into a highly toxic strain (PAR-PFF). Both depletion and inhibition of PARP1 significantly inhibit PFF-induced neurodegeneration (Science 2018). By studying misfolded protein/peptide structures and using biophysical methods, the team identified the amino acid sequence and core-β-sheet hairpin domains (JACS 2013; PNAS 2011).

Mao also studies how aging and environmental factors are strongly correlated with prion-like proteinopathies. Using advanced technologies, including prion-like spread and parabiosis models, high-throughput screening platforms, protein misfolding cyclic amplification, nanobody (Nat Comm 2022), PROTAC, RIBOTAC, nanomaterials (Nano Today 2021), compound and protein microarray, atmospheric chemistry, and analysis, and etc, Mao is exploring new molecular mechanisms and identifying new agents to prevent aging-related neurological disorders. His team is working with clinicians and pathologists, to develop dementia-related biomarkers.

Xiaobo Mao is an associate professor of neurology at the Institute for Cell Engineering at the Johns Hopkins School of Medicine. He received his bachelor in Macromolecule Material in Beijing Technology and Business University, and Ph.D. in Physical Chemistry from the National Center for Nanoscience and Technology, Chinese Academy of Sciences, China. He then came to Johns Hopkins where he completed a postdoc fellowship and assistant Professor in Neurology, Institute for Cell Engineering.